Lien L M, Lee H C, Wang K L, Chiu J C, Chiu H C, Wei Y H
Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Shih Lin, Taipei, Taiwan.
Acta Neurol Scand. 2001 Mar;103(3):159-65. doi: 10.1034/j.1600-0404.2001.103003159.x.
The A3243G mutation of mitochondrial DNA (mtDNA) has been associated with maternally inherited diabetes and deafness (MIDD) in a number of reports; however, the involvement of the nervous system has rarely been mentioned, prompting this exploration of the manifestation of neurological disorders in MIDD cases.
We investigated four generations of a large Taiwanese family in which MIDD is manifest. We conducted a series of clinical examinations, including computed tomography (CT) and magnetic resonance imaging (MRI) of the head, brain 99mTc-HMPAO single photon emission computed tomography (SPECT), cognitive function tests, and nerve conduction velocity (NCV) studies. Blood levels of creatine kinase (CK) and lactate, pathology of muscle biopsy samples and proportions of mutant mtDNA in blood cells, hair follicles, muscle and skin were also analyzed. Mean follow-up period was 4 years.
The patients exhibited the clinical features of diabetes mellitus including sensorineural hearing loss, short stature, and/or histories of spontaneous abortion. No stroke-like episodes were reported. Analysis for mtDNA revealed that the A3243G mutation existed in 11 members (6 symptomatic and 5 asymptomatic members) of this MIDD-prone family, with the proportion of mutant mtDNA ranging from 21% to 47% in leukocytes. Head CT revealed diffuse brain atrophy for all 6 (100%) patients examined and bilateral basal ganglia calcification in 4 of 6 (67%) patients. Brain 99mTc-HMPAO SPECT revealed diminished uptake in the bilateral parieto-occipital or occipital regions for all 6 tested patients, cognitive function for these patients was normal. Results of head CT and SPECT were normal in one asymptomatic member of the family. One muscle biopsy revealed abundant ragged-red fibers with modified Gomori-trichrome stain. Muscle-enzyme activity and serum-lactate levels were normal.
We have demonstrated that a wide spectrum of sub clinical pathologies of the central nervous system and muscle are present for this MIDD-prone family, none of whom developed typical MELAS during the 4-year period of follow-up study.
多项报告表明，线粒体DNA（mtDNA）的A3243G突变与母系遗传的糖尿病和耳聋（MIDD）有关；然而，神经系统受累情况很少被提及，这促使我们对MIDD病例中的神经障碍表现进行探索。
我们调查了一个患有MIDD的大型台湾家庭的四代人。我们进行了一系列临床检查，包括头部计算机断层扫描（CT）和磁共振成像（MRI）、脑99mTc - HMPAO单光子发射计算机断层扫描（SPECT）、认知功能测试以及神经传导速度（NCV）研究。还分析了血液中肌酸激酶（CK）和乳酸水平、肌肉活检样本的病理情况以及血细胞、毛囊、肌肉和皮肤中突变mtDNA的比例。平均随访期为4年。
患者表现出糖尿病的临床特征，包括感音神经性听力损失、身材矮小和/或自然流产史。未报告类似中风的发作。对mtDNA的分析显示，这个易患MIDD的家庭中有11名成员（6名有症状成员和5名无症状成员）存在A3243G突变，白细胞中突变mtDNA的比例在21%至47%之间。头部CT显示，所有6名（100%）接受检查的患者均有弥漫性脑萎缩，6名患者中有4名（67%）出现双侧基底节钙化。脑99mTc - HMPAO SPECT显示，所有6名接受测试的患者双侧顶枕叶或枕叶区域摄取减少，这些患者的认知功能正常。该家庭的一名无症状成员的头部CT和SPECT结果正常。一次肌肉活检显示改良Gomori三色染色有大量破碎红纤维。肌肉酶活性和血清乳酸水平正常。
我们已经证明，这个易患MIDD的家庭存在广泛的中枢神经系统和肌肉亚临床病理情况，在4年的随访研究期间，他们中没有人发展为典型的MELAS。
